Research Perspective Volume 3, Issue 8 pp 803—812

Figure 1. Schematic representation of generation of Aβ by proteolytic processing of APP and the familial AD causing APP mutations. (A) Two pathways (β/γ and α/γ) of APP proteolysis. APP can be cleaved by either β- or α-secretase, which is then followed by γ-secretase cleavage results in the generation of either the p3-fragment (non-amyloidogenic) or an Aβ (amyloigenic pathway). The designation of secretases, substrates and products are depicted, (B) Representation of APP familial AD causing mutations that are identified around N- and C-terminal and in the middle region of Aβ. The amino acid residues are numbered according to Aβ sequence. The swedish mutation (KM>NL) at N-terminus of Aβ̣ near to β-secretase cleavage site increases the total production of Aβ, whereas the mutations C-terminus of Aβ results in increased production of Aβ42 by altering γ-secretase activity. The mutations in the middle region of Aβ might decrease the α-secretory cleavage, facilitate the amyloidogenic processing, promote the Aβ production and/or increases the propensity of Aβ aggregation or stabilizes the Aβ against clearance by different proteases.